A Highly Unusual Palindromic Transmembrane Helical Hairpin Formed by SARS Coronavirus E Protein

Abstract

The agent responsible for the recent severe acute respiratory syndrome (SARS) outbreak is a previously unidentified coronavirus. While there is a wealth of epidemiological studies, little if any molecular characterization of SARS coronavirus (SCoV) proteins has been carried out. Here we describe the molecular characterization of SCoV E protein, a critical component of the virus responsible for virion envelope morphogenesis. We conclusively show that SCoV E protein contains an unusually short, palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature which seems to be unique to SCoV. The hairpin deforms lipid bilayers by way of increasing their curvature, providing for the first time a molecular explanation of E protein's pivotal role in viral budding. The molecular understanding of this critical component of SCoV may represent the beginning of a concerted effort aimed at inhibiting its function, and consequently, viral infectivity.

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A Novel Heavy‐Atom Label for Side‐Specific Peptide Iodination: Synthesis, Membrane Incorporation and X‐ray Reflectivity

“…[17] To detect a single iodine label via difference analysis of the electron density curves of labeled and unlabeled peptides, very high peptide-to-lipid ratios are often required-in the range of P/L % 1/10. [13,16] The necessity for an iodine label improvement has been recognized at least for two reasons. First, there are many transmembrane peptides, especially those connected to an inner and outer membrane domain, that are not at all or only hardly reconstitutable within the membrane environment at such high P/L ratios.…”

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“…Small envelope (E) proteins are structurally conserved within different coronavirus groups, yet exhibit little sequence similarity among these groups [1,73]. In general, coronavirus E proteins are small proteins (varying in size from 76 to 109 amino acids), with an unusually long hydrophobic stretch (25-30 residues) located in between hydrophilic N and C terminus (~8 and ~ 40 residues respectively).…”

“…The unusual length of the hydrophobic segment of SARS-CoV E protein has posed a problem with respect to assigning the topology to the protein. Arbely et al [73] presented a detailed structural model for SARS-CoV E protein, which determined the topology of the protein and the effects upon the lipid bilayer thereof. The results showed that SARS-CoV E protein contains an unusually short palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature that seems to be unique to SARS-CoV.…”